Functionalized metal–organic framework-based photosensitive hydrogel eye drops for inhibition of corneal neovascularization and promotion of epithelial repair

BACKGROUND: Corneal neovascularization is a common pathological feature of various corneal disorders, often leading to severe visual impairment or blindness. Current therapeutic approaches are limited by low bioavailability and considerable side effects. The development of corneal neovascularization is closely associated with inflammatory responses, which not only promote aberrant vascular growth but also compromise corneal epithelial integrity. During this process, rapid responses from corneal epithelial and immune cells result in the release of cytokines and chemokines, influencing tissue repair. Therefore, effective modulation of inflammation and restoration of epithelial structure are critical for the prevention and treatment of corneal neovascularization. METHODS: In this study, we developed a multifunctional photosensitive adhesive hydrogel eye drop, GelMA-OHA/ZIF8@BMP4. The hydrogel was constructed from an interpenetrating network of methacrylated gelatin and oxidized hyaluronic acid, with bone morphogenetic protein 4 encapsulated within zeolitic imidazolate framework-8 nanoparticles to enable sustained release. The multifunctional therapeutic effects of GelMA-OHA/ZIF8@BMP4 were evaluated in vitro, along with its regulatory effects on the PI3K/Akt and TGF-β signaling pathways. In vivo, a rat corneal neovascularization model was employed to assess the effects of GelMA-OHA/ZIF8@BMP4 on neovascular length and area, corneal edema, epithelial cell proliferation, and corneal ultrastructure, including microvilli, intercellular junctions, superficial epithelial layers, and the basement membrane. RESULTS: GelMA-OHA/ZIF8@BMP4 demonstrated potent multifunctional therapeutic effects in vitro, effectively modulating PI3K/Akt and TGF-β signaling. In vivo, GelMA-OHA/ZIF8@BMP4 significantly reduced neovascular length and area, alleviated corneal edema, suppressed abnormal epithelial proliferation, and restored corneal ultrastructure, indicating effective inhibition of inflammatory responses and protection of epithelial integrity. CONCLUSION: GelMA-OHA/ZIF8@BMP4 prevents corneal neovascularization formation through suppression of inflammation and promotion of epithelial repair, exhibiting favorable therapeutic efficacy and safety. This study underscores the potential of a controlled-release hydrogel strategy, independent of exogenous cells or growth factors, for the treatment of inflammation-associated corneal disorders.